Evolocumab Has No Effect on Cognition in Patients Attaining Very Low Levels of LDL Cholesterol

The use of evolocumab, a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor, is not associated with adverse cognitive effects even when low low-density lipoprotein (LDL) cholesterol levels have been achieved, according to results from a subanalysis published in the New England Journal of Medicine.1

Investigators evaluated 1204 patients from the randomized Evaluating PCSK9 Binding Antibody Influence on Cognitive Health in High Cardiovascular Risk Subjects (EBBINGHAUS) study, a subanalysis of the Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER) trial, who received either evolocumab added to statin therapy or placebo. Specifically, the researchers wished to assess the effects of using evolocumab and statin therapy on cognition by using the Cambridge Neuropsychological Test Automated Battery.

Changes in the raw score for the spatial working memory strategy index of executive function in the evolocumab and placebo groups were −0.21±2.62 and −0.29±2.81, respectively (P <.001 for noninferiority; P =.85 for superiority). The investigators found no between-group differences in score changes for working memory (evolocumab, −0.52; placebo, −0.93), episodic memory (evolocumab, −1.53; placebo, −1.53), or psychomotor speed (evolocumab, 5.2 msec; placebo, 0.9 msec). An exploratory analysis found no associations between adverse cognitive outcomes and LDL cholesterol levels, even in patients with LDL cholesterol levels <25 mg/dL.

The researchers noted that a potential limitation to the study was its short follow-up period. Another limitation cited was the exclusion of patients with mild cognitive impairment or dementia.

Despite concern that PCSK9 inhibitors may lead to cognitive deficits due to low levels of LDL cholesterol, this study demonstrated that “evolocumab, as compared with placebo, neither improved nor worsened executive function, working memory, episodic memory, or psychomotor speed.”